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Kidney Week

Abstract: TH-PO1227

Potravitug for the Treatment of BK Polyomavirus Infection in Kidney Transplant Recipients: A Phase II, Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Session Information

Category: Transplantation

  • 2102 Transplantation: Clinical

Authors

  • Wojciechowski, David, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Haririan, Abdolreza, University of Maryland Baltimore, Baltimore, Maryland, United States
  • Asch, William S., Yale School of Medicine, New Haven, Connecticut, United States
  • Dadhania, Darshana M., Weill Cornell Medicine, New York, New York, United States
  • Kew, Clifton E., University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
  • Pavlakis, Martha, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Fowler, Kevin John, The Voice of the Patient, Inc, St. Louis, Missouri, United States
  • Beck, Juergen, Memo Therapeutics AG, Schlieren, ZH, Switzerland
  • Costa, Nadiesda, MedStar Georgetown University Hospital, Washington, District of Columbia, United States
Background

BK polyomavirus (BKPyV) DNAemia is common after kidney transplantation and is often associated with PyV-associated nephropathy. Currently no FDA-approved therapies are available.

Methods

In this phase II randomized, double-blind, placebo-controlled, multicenter trial, safety and efficacy of potravitug was evaluated in kidney transplant recipients (KTRs) with BKPyV DNAemia (>10,000 or 2x >1,000 copies/mL). Participants received four doses of 1000 mg or 500 mg potravitug, or placebo at 4-week intervals, with 42, 11 and 42 patients, respectively. The study included kidney biopsies at baseline and at week 20. The primary endpoint was undetectable DNAemia (LLOQ: <21.5 IU/mL) at week 20. Patients were followed through week 38.

Results

Below LLOQ was observed in 17.5% and 12.9% for potravitug 1000mg and placebo at week 20 (adjusted OR 1.52 [95%CI 0.37-6.27], and 24.3% and 12.9% (OR 3.11 [0.68-14.26]) at week 38. Potravitug 1000 mg showed a higher composite virologic response, defined as >1 log10 decline or <LLOQ in DNAemia in the absence of BKPyVAN: 57.2% vs placebo (33.4%) (adjusted OR 2.79 [1.00-7.75]; nominal p=0.05). While biopsy proven BKPyVAN in the potravitug arm dropped from 51.2% at baseline to 31.6% at week 20; no change was seen in placebo group (23.8% to 24.4%). Less than 2 log10 reductions occurred in 35.6 vs. 22.5% (adjusted OR 1.93 [0.67-5.54]) at week 20 and in 40.3 vs 24.7% (OR 2.11 [0.76-5.88]) at week 38 in the potravitug and placebo groups, respectively. Similar immunosuppression dose changes and frequency were observed in both groups. In the subgroup with patients with stable immunosuppression through week 20, the median DNAemia was lowered from 4.2 at baseline to 3.1 log10 IU/mL at week 20 in potravitug (n=12) vs 3.9 to 3.6 for placebo (n=10). There were no treatment-related Serious Adverse Events or withdrawals due to adverse events.

Conclusion

These phase-II results demonstrate sustained benefit of potravitug in KTRs with significant reduction in DNAema and resolution of biopsy-proven BKPyVAN by week 20, supporting the role of potravitug as the first targeted therapy in KTRs to improve viral clearance and kidney allograft outcome.

Funding

  • Commercial Support – Memo Therapeutics AG

Digital Object Identifier (DOI)